PROJECT ABSTRACT Although aromatase inhibitors (AIs) are the most effective therapy to increase disease-free survival in postmenopausal women with estrogen receptor positive breast cancer, nearly half of patients receiving AIs report debilitating musculoskeletal symptoms, such as joint pain and stiffness, as adverse effects. These symptoms negatively impact patients' quality of life and cause poor adherence to and self-discontinuation of medication, potentially resulting in higher rates of morbidity and mortality. Despite the frequent occurrence of AI-associated musculoskeletal symptom (AIMSS), the mechanism(s) underlying development of AIMSS are poorly understood, and many patients experience unremitting symptoms. Given that many chronic musculoskeletal pain disorders are attributed to central pain dysregulation, the development of AIMSS may be a consequence of central sensitization. While recent animal studies indicate that AI treatment is potentially associated with both peripheral and central sensitization, to date, few investigators have focused on peripheral and central sensitization in relation to the development and/or persistence of AIMSS in breast cancer survivors. Therefore, the proposed F32 training award will address the following specific aims: 1. To evaluate the feasibility by the (a) recruitment, (b) retention, (c) acceptability of subject burden, and (d) appropriateness of dependent and independent variables; and, 2. To examine the underlying mechanisms by investigating (a) the association of altered central pain processing with the presence and symptomatic severity of AIMSS and (b) psychological and genetic contributions to AIMSS. To address these aims, in a prospective, longitudinal study design, 40 participants will undergo the assessment of responses to well-controlled, experimental pain stimuli (i.e. quantitative sensory testing [QST]) and clinical outcome measures of musculoskeletal symptoms and psychological distress (e.g., coping strategy, pain vigilance, pain catastrophizing, anxiety), and the determination of catechol-O-methyltransferase (COMT) variants using saliva samples prior to the AI therapy (i.e. baseline) and at 3- and 6-months after initiating AI therapy. Results from this study will provide important feasibility data for this ongoing program of research, addressing a significant and understudied health concern, AIMSS, in women treated for breast cancer. The proposed investigation and training program will leverage the dissertation work and contribute to my ongoing research and dissemination activities allowing for an ideal training environment.